Dual-responsive choline phosphorylated chitosan hydrogel drives antibacterial-angiogenic synergy in diabetic wound healing.

Wound healing in diabetic patients remains a significant clinical challenge, primarily due to bacterial infections, prolonged inflammation, insufficient angiogenesis, and impaired collagen regeneration. To address these issues, hydrogels with excellent biocompatibility have been widely applied in diabetic wound healing. However, most hydrogels possess only single functionality, limiting their broader clinical application. In this study, we innovatively grafted choline phosphate onto chitosan (MCS), significantly enhancing its hydrophilicity, and combined it with silk fibroin and polyvinyl alcohol to develop a dual-responsive hydrogel dressing with mechanical properties similar to human skin (MCS/SF/PVA/PDA@TH-EGF). To effectively combat the complex bacterial infections associated with diabetic wounds, we incorporated tetracycline hydrochloride-loaded polydopamine nanoparticles into the hydrogel, demonstrating significant antibacterial activity. Furthermore, the addition of recombinant human epidermal growth factor substantially enhances the hydrogel's ability to promote angiogenesis. This MCS/SF/PVA/PDA@TH-EGF hydrogel not only exhibits excellent hydration but also enables precise drug release through near-infrared and pH dual-responsive mechanisms. Based on the specific interactions between MCS and cells, the MCS/SF/PVA/PDA@TH-EGF hydrogel facilitates the adhesion, proliferation, and tube formation of human umbilical vein endothelial cells via "choline phosphate-phosphatidylcholine" interactions. In conclusion, this study presents an innovative hydrogel dressing by modifying chitosan to improve hydrophilicity and incorporating a multifunctional drug release system, which effectively addresses both antibacterial activity and angiogenesis promotion in diabetic wound healing. This work lays a solid theoretical foundation for future clinical applications and advancements in this field.